We have shown major changes in the crystallins and other proteins in the lenses of transgenic mice in which the HIV-1 protease is linked to the alpha A-crystallin promoter from lens. The changes in the protein content of the lens begin around day 20. The homozygous animals get cataracts on day 23 to 24 after birth. The work has shown that the HIV-1 protease activates cysteine protease(s) and this protease cleaves the lens proteins. Thus, the HIV-1 protease is responsible for the activation of the cataract process but not responsible for the subsequent opacification of the lens which is caused by cysteine protease. A delay in cataract formation can be demonstrated in organ culture if a specific inhibitor of cysteine protease is added. These results have been the first clear demonstration that one can separate the initiation of cataract formation from subsequent opacification of the lens. We have also been able to show that the proteins within the lens do not have to undergo major aggregation with the formation of heavy molecular weight aggregates for cataract formation to occur. It had previously been thought that the heavy molecular aggregate formation was essential to opacification of the lens. Biophysical determinations using light scatter on the lenses of these transgenic animals are consistent with this finding. We have thus made two important findings by using this transgenic model. First, the opacification of the lens can be separated from the initiation of cataract formation, and secondly that all cataracts do not necessarily have to form heavy molecular weight aggregates in the process of cataract formation.